Melatonin Prevents Death of Neuroblastoma Cells Exposed to the Alzheimer Amyloid Peptide

Pappolla, Miguel A.; Sos, Melisa; Omar, Rawhi A.; Bick, Roger J.; Hickson-Bick, Diane L. M.; Reiter, Russel J.; Efthimiopoulos, Spiros; Robakis, Nickolaos K.

doi:10.1523/jneurosci.17-05-01683.1997

Cited by 359Circadian rhythm and melatoninAlzheimer's disease research and treatmentsParkinson's Disease Mechanisms and Treatments

Melatonin Prevents Death of Neuroblastoma Cells Exposed to the Alzheimer Amyloid Peptide

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Pappolla, Miguel A., Sos, Melisa, Omar, Rawhi A., Bick, Roger J., Hickson-Bick, Diane L. M., Reiter, Russel J., Efthimiopoulos, Spiros, Robakis, Nickolaos K.·1997·The Journal of Neuroscience

DOI 10.1523/jneurosci.17-05-01683.1997PMC PMC6573387

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Abstract

Studies from several laboratories have generated evidence suggesting that oxidative stress is involved in the pathogenesis of Alzheimer's disease (AD). The finding that the amyloid beta protein (Abeta) has neurotoxic properties and that such effects are, in part, mediated by free radicals has provided insights into mechanisms of cell death in AD and an avenue to explore new therapeutic approaches. In this study we demonstrate that melatonin, a pineal hormone with recently established antioxidant properties, is remarkably effective in preventing death of cultured neuroblastoma cells as well as oxidative damage and intracellular Ca2+ increases induced by a cytotoxic fragment of Abeta. The effects of melatonin were extremely reproducible and corroborated by multiple quantitative methods, including cell viability studies by confocal laser microscopy, electron microscopy, and measurements of intracellular calcium levels. The importance of this finding is that, in contrast to conventional antioxidants, melatonin has a proposed physiological role in the aging process. Secretion levels of this hormone are decreased in aging and more severely reduced in AD. The reported phenomenon may be of therapeutic relevance in AD.

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Antioxidants protect against amyloid-beta induced neuronal toxicity.
“Studies have also reported that antioxidants protect against Aβ induced neuronal toxicity [16,17].”
From Indian Medicinal Herbs and Formulations for Alzheimer’s Disease, from Traditional Knowledge to Scientific Assessment (2020) · cites this paper as [17]

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A novel assay for apoptosis Flow cytometric detection of phosphatidylserine expression on early apoptotic cells using fluorescein labelled Annexin V
Vermes, I., Haanen, C., Steffens-Nakken, H. M., & Reutellingsperger, C. (1995) · Journal of Immunological Methods · doi:10.1016/0022-1759(95)00072-i · Cited by 5,437 · see citing works
Alzheimer's disease: Initial report of the purification and characterization of a novel cerebrovascular amyloid protein
Glenner, G. G., & Wong, C. W. (1984) · Biochemical and Biophysical Research Communications · doi:10.1016/s0006-291x(84)80190-4 · Cited by 5,404 · see citing works
Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease
Goate, A., Chartier-Harlin, M.-C., Mullan, M., Brown, J., Crawford, F., Fidani, L., Giuffra, L., Haynes, A., Irving, N., James, L., et al. (1991) · Nature · doi:10.1038/349704a0 · Cited by 4,659 · see citing works
Annexin V for flow cytometric detection of phosphatidylserine expression on B cells undergoing apoptosis
Koopman, G., Reutelingsperger, C. P. M., Kuijten, G., Keehnen, R. M. J., Pals, S. T., & van Oers, M. H. J. (1994) · Blood · doi:10.1182/blood.v84.5.1415.1415 · Cited by 2,687 · see citing works
Hydrogen peroxide mediates amyloid β protein toxicity
Behl, C. (1994) · Cell · doi:10.1016/0092-8674(94)90131-7 · Cited by 2,074 · see citing works
Annexin V for flow cytometric detection of phosphatidylserine expression on B cells undergoing apoptosis
Koopman, G., Reutelingsperger, C., Kuijten, G., et al. (1994) · Blood · doi:10.1182/blood.v84.5.1415.bloodjournal8451415 · Cited by 2,068 · see citing works
Neurotrophic and Neurotoxic Effects of Amyloid β Protein: Reversal by Tachykinin Neuropeptides
Yankner, B. A., Duffy, L. K., & Kirschner, D. A. (1990) · Science · doi:10.1126/science.2218531 · Cited by 1,975 · see citing works
Amyloid β-peptide is produced by cultured cells during normal metabolism
Haass, C., Schlossmacher, M. G., Hung, A. Y., Vigo-Pelfrey, C., Mellon, A., Ostaszewski, B. L., Lieberburg, I., Koo, E. H., Schenk, D., Teplow, D. B., et al. (1992) · Nature · doi:10.1038/359322a0 · Cited by 1,921 · cited 1× · see citing works
“Ab also is produced during normal cellular metabolism (Haass et al., 1992; Shoji et al., 1992).”
Background
beta-Amyloid peptides destabilize calcium homeostasis and render human cortical neurons vulnerable to excitotoxicity
Mattson, M. P., Cheng, B., Davis, D. G., Bryant, K., Lieberburg, I. M., & Rydel, R. E. (1992) · Journal of Neuroscience · doi:10.1523/jneurosci.12-02-00376.1992 · Cited by 1,627 · cited 1× · see citing works
“In addition to free radicals, increased sensitivity to excitotoxicity (Copani et al., 1995) and /or disruption of Ca 2ϩ homeostasis (Mattson et al., 1992, 1993; Le et al., 1995; Mark et al., 1995) seem to be involved.”
Background
Fluorescent indicators for cytosolic calcium based on rhodamine and fluorescein chromophores
Minta, A., Kao, J. P. Y., & Tsien, R. Y. (1989) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)83165-9 · Cited by 1,621 · cited 2× · see citing works
“The fluorescent probe fluo-3 was used for measurements of Ca(21) as described (Minta et al., 1985).”
Method
Production of the Alzheimer Amyloid β Protein by Normal Proteolytic Processing
Shoji, M., Golde, T. E., Ghiso, J., Cheung, T. T., Estus, S., Shaffer, L. M., Cai, X.-D., McKay, D. M., Tintner, R., Frangione, B., et al. (1992) · Science · doi:10.1126/science.1439760 · Cited by 1,447 · see citing works
Neurodegeneration induced by beta-amyloid peptides in vitro: the role of peptide assembly state
Pike, C., Burdick, D., Walencewicz, A., Glabe, C., & Cotman, C. (1993) · The Journal of Neuroscience · doi:10.1523/jneurosci.13-04-01676.1993 · Cited by 1,417 · see citing works
Identification, biogenesis, and localization of precursors of Alzheimer's disease A4 amyloid protein
Weidemann, A., König, G., Bunke, D., Fischer, P. Q., Salbaum, J. M., Masters, C. L., & Beyreuther, K. T. (1989) · Cell · doi:10.1016/0092-8674(89)90177-3 · Cited by 1,233 · see citing works
Early-onset Alzheimer's disease caused by mutations at codon 717 of the β-amyloid precursor protein gene
Chartier-Harlin, M.-C., Crawford, F., Houlden, H., Warren, A., Hughes, D., Fidani, L., Goate, A., Rossor, M., Roques, P., Hardy, J., et al. (1991) · Nature · doi:10.1038/353844a0 · Cited by 1,214 · see citing works
A model for beta-amyloid aggregation and neurotoxicity based on free radical generation by the peptide: relevance to Alzheimer disease.
Hensley, K., Carney, J. M., Mattson, M. P., Aksenova, M., Harris, M., Wu, J. F., Floyd, R. A., & Butterfield, D. A. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.8.3270 · Cited by 1,086 · cited 1× · see citing works
“in AD (Hensley et al., 1994; Mattson, 1994; Pappolla et al., 1996).”
Background
Assembly and aggregation properties of synthetic Alzheimer's A4/beta amyloid peptide analogs.
Burdick, D., Soreghan, B., Kwon, M., Kosmoski, J., Knauer, M., Henschen, A., Yates, J., Cotman, C., & Glabe, C. (1992) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)48529-8 · Cited by 1,014 · cited 2× · see citing works
“, 1993), time of exposure, osmolarity, pH, and concentration (Burdick et al., 1992; Pike et al., 1993).”
Background
Molecular cloning and characterization of a cDNA encoding the cerebrovascular and the neuritic plaque amyloid peptides.
Robakis, N. K. R. K., Ramakrishna, N., Wolfe, G. C., & Wisniewski, H. M. (1987) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.84.12.4190 · Cited by 603 · see citing works
Vitamin E protects nerve cells from amyloid βprotein toxicity
Behl, C., Davis, J. B., Cole, G. M., & Schubert, D. A. (1992) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(92)90837-b · Cited by 582 · see citing works
Amyloid beta-peptide impairs ion-motive ATPase activities: evidence for a role in loss of neuronal Ca2+ homeostasis and cell death
Mark, R. J., Hensley, K., Butterfield, D. A., & Mattson, M. P. (1995) · Journal of Neuroscience · doi:10.1523/jneurosci.15-09-06239.1995 · Cited by 553 · cited 4× · see citing works
“characteristic targets of oxidative injury (Rohn et al., 1993), and damage to these structures by Abhas been documented ( Mark et al., 1995 ).”
BackgroundInfluential
Calcium-Mediated Mechanisms in Chemically Induced Cell Death
Nicotera, P., Bellomo, G., & Orrenius, S. (1992) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pa.32.040192.002313 · Cited by 519 · cited 2× · see citing works
“Abnormal efflux of the ion into cellular compartments (Nicotera et al., 1992) causes activation of a number of Ca(21)-dependent degradative processes detrimental to the cell.”
Background
β-Amyloid precursor protein metabolites and loss of neuronal Ca2+ homeostasis in Alzheimer's disease
Mattson, M. P., Barger, S. W., Cheng, B., Lieberburg, I. M., Smith‐Swintosky, V. L., & Rydel, R. E. (1993) · Trends in Neurosciences · doi:10.1016/0166-2236(93)90009-b · Cited by 516 · cited 1× · see citing works
“In addition to free radicals, increased sensitivity to excitotoxicity (Copani et al., 1995) and /or disruption of Ca 2ϩ homeostasis (Mattson et al., 1992, 1993; Le et al., 1995; Mark et al., 1995) seem to be involved.”
Background
Interfering with Apoptosis: Ca 2+ -Binding Protein ALG-2 and Alzheimer's Disease Gene ALG-3
Vito, P., Lacaná, E., & D'adamio, L. (1996) · Science · doi:10.1126/science.271.5248.521 · Cited by 468 · see citing works
Secreted Forms of β-Amyloid Precursor Protein Protect Hippocampal Neurons against Amyloid β-Peptide-Induced Oxidative Injury
Goodman, Y., & Mattson, M. P. (1994) · Experimental Neurology · doi:10.1006/exnr.1994.1107 · Cited by 449 · see citing works
Heme oxygenase-1 is associated with the neurofibrillary pathology of Alzheimer's disease.
Smith, M. A., Kutty, R. K., Richey, P. L., Yan, S. D., Stern, D., Chader, G. J., Wiggert, B. O., Petersen, R. B., & Perry, G. L. (1994) · PubMed Central · Cited by 425 · see citing works
β-Amyloid Peptide Free Radical Fragments Initiate Synaptosomal Lipoperoxidation in a Sequence-Specific Fashion: Implications to Alzheimer′s Disease
Butterfield, D. A., Hensley, K., Harris‐White, M. E., Mattson, M. P., & Carney, J. M. (1994) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1994.1508 · Cited by 404 · see citing works
Age-Dependent Reduction in Serum Melatonin Concentrations in Healthy Human Subjects
Iguchi, H., Kato, K., & Ibayashi, H. (1982) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-55-1-27 · Cited by 381 · cited 2× · see citing works
“On one hand, melatonin has a proposed physiological role in the aging process (Pierpaoli , 1991; Pierpaoli et al., 1991), and decreased secretion of melatonin with aging is documented (Iguchi et al., 1982; Dori et al., 1994).”
Background
Immunohistochemical evidence of oxidative [corrected] stress in Alzheimer's disease.
Pappolla, M. A., Omar, R. A., Kim, K. S., & Robakis, N. K. R. K. (1992) · PubMed Central · Cited by 363 · see citing works
Morning bright light therapy for sleep and behavior disorders in elderly patients with dementia
Mishima, K., Okawa, M., Hishikawa, Y., Hozumi, S., Hori, H., & Takahashi, K. (1994) · Acta Psychiatrica Scandinavica · doi:10.1111/j.1600-0447.1994.tb01477.x · Cited by 334 · cited 2× · see citing works
“study, there are reports of more profound reductions of melatonin secretion in populations with dementia than in nondemented controls (Souetre et al., 1989; Mishima et al., 1994).”
BackgroundResult
Direct evidence of oxidative injury produced by the Alzheimer's β-Amyloid peptide (1–40) in cultured hippocampal neurons
Harris‐White, M. E., Hensley, K., Butterfield, D. A., Leedle, R. A., & Carney, J. M. (1995) · Experimental Neurology · doi:10.1016/0014-4886(95)90041-1 · Cited by 331 · see citing works
Basic Techniques for Transmission Electron Microscopy
(1986) · Elsevier eBooks · doi:10.1016/b978-0-12-333926-3.x5001-5 · Cited by 328 · see citing works
Nuclear localization of melatonin in different mammalian tissues: Immunocytochemical and radioimmunoassay evidence
Menéndez-Peláez, A., Pöeggeler, B., Reiter, R. J., Barlow‐Walden, L., Pablos, M. I., & Tan, D.-X. (1993) · Journal of Cellular Biochemistry · doi:10.1002/jcb.240530415 · Cited by 325 · cited 2× · see citing works
“In vivo studies have shown that melatonin rapidly crosses the blood–brain barrier after systemic administration and reaches every neuronal compartment (Menendez-Pelaez et al., 1993).”
Background
Chronic inhibition of superoxide dismutase produces apoptotic death of spinal neurons.
Rothstein, J. D., Bristol, L. A., Hosler, B. A., Brown, R. H., & Kuncl, R. W. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.10.4155 · Cited by 292 · see citing works
The pineal gland and melatonin in relation to aging: A summary of the theories and of the data
Reiter, R. J. (1995) · Experimental Gerontology · doi:10.1016/0531-5565(94)00045-5 · Cited by 286 · cited 2× · see citing works
“Initial in vitro evidence suggests that the cytoprotective effects of melatonin are related to its antioxidant properties (Reiter, 1995).”
BackgroundResult
Daily variation in the concentration of melatonin and 5-methoxytryptophol in the human pineal gland: effect of age and Alzheimer's disease
Skene, D. J., VIVIEN‐ROELS, B., Sparks, D. L., Hunsaker, J. C., Pévet, P., Ravid, D., & Swaab, D. F. (1990) · Brain Research · doi:10.1016/0006-8993(90)90214-v · Cited by 224 · see citing works
Calmodulin mediates melatonin cytoskeletal effects
Benítez‐King, G., & Antón‐Tay, F. (1993) · Cellular and Molecular Life Sciences · doi:10.1007/bf01923944 · Cited by 222 · see citing works
Amyloid β peptide induces necrosis rather than apoptosis
Behl, C., Davis, J. B., Klier, F. G., & Schubert, D. (1994) · Brain Research · doi:10.1016/0006-8993(94)91659-4 · Cited by 219 · see citing works
Exact cleavage site of Alzheimer amyloid precursor in neuronal PC-12 cells
Anderson, J. P., Esch, F. S., Keim, P. S., Sambamurti, K., Lieberburg, I. M., & Robakis, N. K. R. K. (1991) · Neuroscience Letters · doi:10.1016/0304-3940(91)90775-o · Cited by 212 · see citing works
Rapid Communication: Ca2+ Channel Blockers Attenuate β‐Amyloid Peptide Toxicity to Cortical Neurons in Culture
Weiss, J. H., Pike, C. J., & Cotman, C. W. (1994) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1994.62010372.x · Cited by 211 · see citing works
Methodological variables in the assessment of beta amyloid neurotoxicity
Busciglio, J. A., Lorenzo, A., & Yankner, B. A. (1992) · Neurobiology of Aging · doi:10.1016/0197-4580(92)90065-6 · Cited by 210 · cited 2× · see citing works
“demonstrated that the effects of the peptide are dependent on aggregation (Busciglio et al., 1992; Pike et al., 1993), time of exposure, osmolarity, pH, and concentration (Burdick et al.”
Background
Apoptotic Cell Death Induced by β‐Amyloid1–42 Peptide Is Cell Type Dependent
Gschwind, M., & Huber, G. (1995) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1995.65010292.x · Cited by 201 · cited 2× · see citing works
“Although apoptosis is defined by more than one single feature, we used this method as one additional indicator of the phenomenon reported here [whether Ab causes apoptosis or necrosis is not the subject of this investigation, although it is reported to depend on cell type (Gschwind and Huber, 1995) and/or Ab concentra…”
BackgroundMethod
Ion transport ATPases as targets for free radical damage
Rohn, T. T., Hinds, T. R., & Vincenzi, F. F. (1993) · Biochemical Pharmacology · doi:10.1016/0006-2952(93)90530-a · Cited by 176 · cited 1× · see citing works
“Sulfhydryl groups in membrane Ca 2ϩ pumps are characteristic targets of oxidative injury (Rohn et al., 1993), and damage to these structures by A␤ has been documented (Mark et al., 1995).”
Background
Activation of metabotropic glutamate receptors protects cultured neurons against apoptosis induced by beta-amyloid peptide.
Copani, A., Bruno, V., Battaglia, G., Leanza, G., Pellitteri, R., Russo, A., Stanzani, S., & Nicoletti, F. (1995) · Molecular Pharmacology · doi:10.1016/s0026-895x(25)08600-6 · Cited by 167 · cited 3× · see citing works
“The magnitude of the damage contributed by each of these factors and the extent of their interaction are unresolved issues (Busciglio et al., 1993; Mattson, 1994; Weiss et al., 1994; Copani et al., 1995).”
Background
Calcium and Neuronal Injury in Alzheimer's Disease
Mattson, M. P. (1994) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1994.tb44401.x · Cited by 164 · cited 3× · see citing works
“It has been proposed that Ca 2ϩ plays an important role in A␤-mediated cell death (Mattson, 1994).”
Background
Apoptosis suppression by bcl-2 is correlated with the regulation of nuclear and cytosolic Ca2+.
Marín, M. C., Fernandez, A., Bick, R. J., Brisbay, S. M., Buja, L. M., Snuggs, M. B., McConkey, D. J., von Eschenbach, A. C., Keating, M. J., & McDonnell, T. J. (1996) · PubMed · Cited by 158 · see citing works
Calcium and neuronal injury in Alzheimer's disease. Contributions of beta-amyloid precursor protein mismetabolism, free radicals, and metabolic compromise.
Mattson, M. P. (1994) · PubMed · Cited by 154 · see citing works
Familial Alzheimer's disease
Feldman, R. G., Chandler, K. A., Levy, L. L., & Glaser, G. H. (1963) · Neurology · doi:10.1212/wnl.13.10.811 · Cited by 152 · see citing works
Localization of superoxide dismutases in Alzheimer's disease and Down's syndrome neocortex and hippocampus.
Furuta, A., Price, D. L., Pardo, C. A., Troncoso, J. C., Xu, Z., Taniguchi, N., & Martin, L. J. (1995) · Europe PMC (PubMed Central) · Cited by 151 · see citing works
The Pineal Control of Aging
Pierpaoli, W., Dall'Ara, A., Pedrinis, E., & Regelson, W. (1991) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1991.tb16987.x · Cited by 150 · cited 1× · see citing works
“On one hand, melatonin has a proposed physiological role in the aging process (Pierpaoli , 1991; Pierpaoli et al., 1991), and decreased secretion of melatonin with aging is documented (Iguchi et al., 1982; Dori et al., 1994).”
Background
Evidence for intracellular cleavage of the Alzheimer's amyloid precursor in PC12 cells
Sambamurti, K., Shioi, J., Anderson, J. P., Pappolla, M. A., & Robakis, N. K. R. K. (1992) · Journal of Neuroscience Research · doi:10.1002/jnr.490330216 · Cited by 144 · see citing works
Cell death induced by β-amyloid 1–40 in MES 23.5 hybrid clone: the role of nitric oxide and NMDA-gated channel activation leading to apoptosis
Le, W., Colom, L. V., Xie, W., SMITH, R. G., Alexianu, M. E., & Appel, S. H. (1995) · Brain Research · doi:10.1016/0006-8993(95)00450-5 · Cited by 138 · cited 4× · see citing works
“Although apoptosis is defined by more than one single feature, we used this method as one additional indicator of the phenomenon reported here [whether Ab causes apoptosis or necrosis is not the subject of this investigation, although it is reported to depend on cell type (Gschwind and Huber, 1995) and/or Ab concentra…”
BackgroundMethodInfluential
Effects of melatonin on microtubule assembly depend on hormone concentration: Role of melatonin as a calmodulin antagonist
Huerto‐Delgadillo, L., Antón‐Tay, F., & Benítez‐King, G. (1994) · Journal of Pineal Research · doi:10.1111/j.1600-079x.1994.tb00114.x · Cited by 132 · cited 1× · see citing works
“In addition to its OFR scavenging properties, melatonin interacts with calmodulin (Benitez-King and Anton-Tay, 1993) microtubular components (Benitez-King and Anton-Tay, 1993) and is reported to increase the activity of the intrinsic cellular antioxidant defenses (Huerto-Delgadillo et al., 1994).”
Background
Flow cytometric analysis of cell cycle‐dependent changes in cell thiol level by combining a new laser dye with hoechst 33342
Poot, M., Kavanagh, T. J., Kang, H. C., Haugland, R. P., & Rabinovitch, P. S. (1991) · Cytometry · doi:10.1002/cyto.990120214 · Cited by 108 · cited 1× · see citing works
“These included fluorescent staining with the probe BODIPY green (Molecular Probes, Eugene, OR), which is a reliable indicator of viability (Poot et al., 1991), dual fluorescent labeling using annexin V-FITC and propidium iodide (R & D Systems, Minneapolis, MN) (Koopman et al., 1994; Vermes et al.,…”
Method
β‐Amyloid Neurotoxicity in Human Cortical Culture Is Not Mediated by Excitotoxins
Busciglio, J. A., Yeh, J., & Yankner, B. A. (1993) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1993.tb13658.x · Cited by 86 · cited 1× · see citing works
“The magnitude of the damage contributed by each of these factors and the extent of their interaction are unresolved issues (Busciglio et al., 1993; Mattson, 1994; Weiss et al., 1994; Copani et al., 1995).”
Background
Oxygen free radicals as inducers of heat shock protein synthesis in cultured human neuroblastoma cells: Relevance to neurodegenerative disease
Omar, R., & Pappolla, M. A. (1993) · European Archives of Psychiatry and Clinical Neuroscience · doi:10.1007/bf02190384 · Cited by 81 · see citing works
Familial Alzheimer's disease A pedigree with a mis-sense mutation in the amyloid precursor protein gene (amyloid precursor protein 717 valine → glycine)
Kennedy, A. M., Newman, S., McCaddon, A., Ball, J. A., Roques, P. K., MULLAN, M. J., Hardy, J., Chartier‐Harlin, M., Frackowiak, R. S. J., Warrington, E. K., et al. (1993) · Brain · doi:10.1093/brain/116.2.309 · Cited by 72 · see citing works
Chrono-neuroendocrinological aspects of physiological aging and senile dementia.
Dori, D., Casale, G., Solerte, S. B., Fioravanti, M., Migliorati, G., Cuzzoni, G., & Ferrari, E. (1994) · PubMed · Cited by 59 · see citing works
Antioxidant enzymes and survival of normal and simian virus 40-transformed mouse embryo cells after hyperthermia.
OMAR, R. A., Yano, S., & Kikkawa, Y. (1987) · PubMed · Cited by 47 · see citing works
The pineal gland: A circadian or seasonal aging clock?
Pierpaoli, W. (1991) · Aging Clinical and Experimental Research · doi:10.1007/bf03323985 · Cited by 32 · see citing works
The heat shock/oxidative stress connection
Pappolla, M. A., Sos, M., Omar, R. A., & Sambamurti, K. (1996) · Molecular and Chemical Neuropathology · doi:10.1007/bf02815201 · Cited by 32 · see citing works
Human cortical neuronal (HCN) cell lines: a model for amyloid β neurotoxicity
Zhang, Z., Drzewiecki, G. J., Hom, J. T., May, P. C., & Hyslop, P. A. (1994) · Neuroscience Letters · doi:10.1016/0304-3940(94)90892-3 · Cited by 27 · see citing works
Abnormal melatonin response to 5-methoxypsoralen in dementia
Souêtre, E., Salvati, E., Krebs, B., Belugou, J. L., & DARCOURT, G. (1989) · American Journal of Psychiatry · doi:10.1176/ajp.146.8.1037 · Cited by 26 · see citing works
Unspecific neurologic symptoms as possible psychogenic complaints
Franz, M., Schepank, H. G. F., & Schellberg, D. (1993) · European Archives of Psychiatry and Clinical Neuroscience · doi:10.1007/bf02191516 · Cited by 6 · see citing works

Flagged first, then by citations

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Research works printed but not linked: 1

Hyman BT, West HL, Gomez-Isla T, Mui S (1985) Quantitative neuro- pathology in Alzheimer's disease: neuronal loss in high-order associa- tion cortex parallels dementia. In: Research advances in Alzheimer's disease and related disorders (Iqbal K, Mortimer JA, Windblad B, Wisniewski HM, eds), pp 453-460. New York: Wiley.

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Christen, Y. (2000) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/71.2.621s · Cited by 1,158 · see citing works
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Galano, A., Tan, D. X., & Reiter, R. J. (2011) · Journal of Pineal Research · doi:10.1111/j.1600-079x.2011.00916.x · Cited by 1,154 · see citing works
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Reiter, R. J. (1998) · Progress in Neurobiology · doi:10.1016/s0301-0082(98)00052-5 · Cited by 836 · see citing works
“In addition, Pappolla et al. (1997c, 1998) have recently found that the aggregation of Ab peptide into b-sheets and amyloid ®brils, which are important for the toxicity of the peptide and renders it resistance to proteolytic degradation, is greatly reduced by melatonin.”
Background
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Hardeland, R. (2005) · Endocrine · doi:10.1385/endo:27:2:119 · Cited by 670 · see citing works
Melatonin: A Multitasking Molecule
Reiter, R. J., Tan, D. X., & Fuentes‐Broto, L. (2010) · Progress in brain research · doi:10.1016/s0079-6123(08)81008-4 · Cited by 642 · see citing works
“This action likely contributes to the ability of melatonin to inhibit the intrinsic pathway of apoptosis and reduce neuronal loss in experimental models of Alzheimer’s disease (AD) (Olcese et al., 2009; Pappolla et al., 1997; Zhou et al., 2008) and Parkinson’s disease (PD) (Chetsawang et al.”
Background
Melatonin mitigates mitochondrial malfunction
León, J., Acuña-Castroviejo, D., Escames, G., Tan, D. X., & Reiter, R. J. (2004) · Journal of Pineal Research · doi:10.1111/j.1600-079x.2004.00181.x · Cited by 515 · see citing works
“Melatonin is also neuroprotective in in vitro models of Alzheimer’s disease through its stimulatory effects on complex V activity [9, 28, 38].”
Background
Mitochondrial Oxidative Stress—A Causative Factor and Therapeutic Target in Many Diseases
Kowalczyk, P., Sulejczak, D., Kleczkowska, P., Bukowska‐Ośko, I., Kucia, M., Popiel, M., Wietrak, E., Kramkowski, K., Wrzosek, K., & Kaczyńska, K. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222413384 · Cited by 528 · see citing works
Mechanisms of homocysteine neurotoxicity in neurodegenerative diseases with special reference to dementia
Obeid, R., & Herrmann, W. (2006) · FEBS Letters · doi:10.1016/j.febslet.2006.04.088 · Cited by 490 · see citing works
“Melatonin prevents oxidative stress and death of neurons exposed to Ab [101,102].”
Background
Potent Neuroprotective Properties against the Alzheimer β-Amyloid by an Endogenous Melatonin-related Indole Structure, Indole-3-propionic Acid
Chyan, Y., Pöeggeler, B., Omar, R., Chain, D. G., Frangione, B., Ghiso, J. A., & Pappolla, M. A. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.31.21937 · Cited by 409 · see citing works
Antiinflammatory Activity of Melatonin in Central Nervous System
Esposito, E., & Cuzzocrea, S. (2010) · Current Neuropharmacology · doi:10.2174/157015910792246155 · Cited by 408 · see citing works
“In vitro experiments showed that A -treated cultures exhibited characteristic features of apoptosis, and melatonin attenuated A -induced apoptosis in a number of cellular models of AD including mouse microglial BV2 cells, rat astroglioma C6 cells, and PC12 cells [43, 52, 54, 145, 225].”
Background
Protective effect of resveratrol on β-amyloid-induced oxidative PC12 cell death
Jang, J.-H. (2003) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(03)00062-5 · Cited by 391 · see citing works
Melatonin, human aging, and age-related diseases
Karasek, M. (2004) · Experimental Gerontology · doi:10.1016/j.exger.2004.04.012 · Cited by 380 · see citing works
The role of oxidative stress in the toxicity induced by amyloid β-peptide in Alzheimer’s disease
Miranda, S., Opazo, C., Larrondo, L. F., Muñoz, F. J., Ruiz, F., Leighton, F., & Inestrosa, N. C. (2000) · Progress in Neurobiology · doi:10.1016/s0301-0082(00)00015-0 · Cited by 369 · see citing works
Melatonin and sleep in aging population
Pandi-Perumal, S. R., Zisapel, N., Srinivasan, V. J., & Cardinali, D. P. (2005) · Experimental Gerontology · doi:10.1016/j.exger.2005.08.009 · Cited by 367 · see citing works
Melatonin: From Basic Research to Cancer Treatment Clinics
Vijayalaxmi, V., Thomas, C. R., Reiter, R. J., & Herman, T. S. (2002) · Journal of Clinical Oncology · doi:10.1200/jco.2002.11.004 · Cited by 358 · see citing works
Inhibition of Alzheimer β-Fibrillogenesis by Melatonin
Pappolla, M. A., Bozner, P., Soto, C. A., Shao, H., Robakis, N. K., Zagorski, M. G., Frangione, B., & Ghiso, J. A. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.13.7185 · Cited by 338 · see citing works
Melatonin increases survival and inhibits oxidative and amyloid pathology in a transgenic model of Alzheimer's disease
Matsubara, E., Bryant‐Thomas, T., Pacheco Quinto, J., Henry, T. L., Poeggeler, B., Herbert, D., Cruz‐Sanchez, F., Chyan, Y., Smith, M. A., Perry, G., et al. (2003) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2003.01654.x · Cited by 332 · see citing works
Melatonin and mitochondrial function
León, J., Acuña-Castroviejo, D., Sainz, R. M., Mayo, J. C., Tan, D., & Reiter, R. J. (2004) · Life Sciences · doi:10.1016/j.lfs.2004.03.003 · Cited by 331 · see citing works
Evidence of oxidative stress and in vivo neurotoxicity of beta-amyloid in a transgenic mouse model of Alzheimer's disease: a chronic oxidative paradigm for testing antioxidant therapies in vivo.
Pappolla, M. A., Chyan, Y., Omar, R. A., Hsiao, K., Perry, G. L., Smith, M. A., & Bozner, P. (1998) · Europe PMC (PubMed Central) · Cited by 328 · see citing works
Melatonin Antioxidative Defense: Therapeutical Implications for Aging and Neurodegenerative Processes
Pandi-Perumal, S. R., BaHammam, A. S., Brown, G. M., Spence, D. W., Bharti, V. K., Kaur, C., Hardeland, R., & Cardinali, D. P. (2012) · Neurotoxicity Research · doi:10.1007/s12640-012-9337-4 · Cited by 320 · see citing works
Melatonin and cell death: differential actions on apoptosis in normal and cancer cells
Sainz, R. M., Mayo, J. C., Rodrı́guez, C., Tan, D. X., López‐Burillo, S., & Reiter, R. J. (2003) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-003-2319-1 · Cited by 305 · see citing works
Alzheimer’s disease: pathological mechanisms and the beneficial role of melatonin
Rosales‐Corral, S., Acuña-Castroviejo, D., Coto‐Montes, A. M., Boga, J. A., Manchester, L. C., Fuentes‐Broto, L., Korkmaz, A., Ma, S., Tan, D. X., & Reiter, R. J. (2011) · Journal of Pineal Research · doi:10.1111/j.1600-079x.2011.00937.x · Cited by 293 · see citing works
“Thus, it is possible to reproduce in vitro mtDNA damage by adding Ab1–42 to neurons in culture, but the addition of melatonin prevents significantly mtDNA damage [14, 347].”
Background
Melatonin rhythmicity: effect of age and Alzheimer's disease
Skene, D. J. (2003) · Experimental Gerontology · doi:10.1016/s0531-5565(02)00198-5 · Cited by 270 · see citing works
Early neuropathological Alzheimer's changes in aged individuals are accompanied by decreased cerebrospinal fluid melatonin levels
Zhou, J., Liu, R., Kamphorst, W., Hofman, M. A., & Swaab, D. F. (2003) · Journal of Pineal Research · doi:10.1034/j.1600-079x.2003.00065.x · Cited by 269 · see citing works
“Melatonin interacts with b-amyloid 1–40 and b-amyloid 1–42 and inhibits the progressive formation of the b-sheets of the amyloid fibrils [6, 8].”
Background
Protection against cognitive deficits and markers of neurodegeneration by long‐term oral administration of melatonin in a transgenic model of Alzheimer disease
Olcese, J., Cao, C., Mori, T., Mamcarz, M. B., Maxwell, A. K., Runfeldt, M. J., Wang, L., Zhang, C., Lin, X., Zhang, G., et al. (2009) · Journal of Pineal Research · doi:10.1111/j.1600-079x.2009.00692.x · Cited by 260 · see citing works
“Transgenic AD mice have been shown to express markers of oxidative stress in the neurons surrounding the Ab plaques that they develop [39, 58].”
Background
Pharmacology and Physiology of Melatonin in the Reduction of Oxidative Stress in vivo
Reiter, R. J., Tan, D., Qi, W., Manchester, L. C., Karbownik‐Lewińska, M., & Calvo, J. R. (2000) · Neurosignals · doi:10.1159/000014636 · Cited by 258 · see citing works
Alzheimer's disease: a re-examination of the amyloid hypothesis
Neve, R. L., & Robakis, N. K. (1998) · Trends in Neurosciences · doi:10.1016/s0166-2236(97)01168-5 · Cited by 261 · see citing works
N 1 ‐acetyl‐ N 2 ‐formyl‐5‐methoxykynuramine, a biogenic amine and melatonin metabolite, functions as a potent antioxidant
Tan, D. X., Manchester, L. C., Burkhardt, S., Sainz, R. M., Mayo, J. C., Kohen, R., Shohami, E., Huo, Y., Hardeland, R., & Reiter, R. J. (2001) · The FASEB Journal · doi:10.1096/fj.01-0309fje · Cited by 253 · see citing works
“In the present study, the cultured neurons were HT22 hippocampal cells; whereas in the study of Pappolla and co-workers (34), neuroblastoma cells were used.”
BackgroundMethod
An assessment of the antioxidant and the antiamyloidogenic properties of melatonin: implications for Alzheimer's disease
Pappolla, M. A., Chyan, Y., Pöeggeler, B., Frangione, B., Wilson, G. L., Ghiso, J. A., & Reiter, R. J. (2000) · Journal of Neural Transmission · doi:10.1007/s007020050018 · Cited by 239 · see citing works
“Also, melatonin has been shown effective in reducing amyloid â-induced lipid peroxidation in vitro (Pappolla et al., 1997; Daniels et al., 1998).”
Background
Role of melatonin in neurodegenerative diseases
Srinivasan, V. J., Pandi-Perumal, S. R., Maestroni, G. J. M., Esquifino, A. I., Hardeland, R., & Cardinali, D. P. (2005) · Neurotoxicity Research · doi:10.1007/bf03033887 · Cited by 232 · see citing works
“Among the various neurodegenerative diseases, it is in AD where the role of melatonin has been thoroughly studied both in experimental models and in patients (Pappolla et al., 1997; 2000; Matsubara et al., 2003).”
BackgroundInfluential
The Antiapoptotic Activity of Melatonin in Neurodegenerative Diseases
Wang, X. (2009) · CNS Neuroscience & Therapeutics · doi:10.1111/j.1755-5949.2009.00105.x · Cited by 232 · see citing works
“The great advance has been currently conduced in studies of protection against AD by antioxidant melatonin inhibiting Aβ-induced toxicity [25,89–93] and attenuating tau hyperphosphorylation [85,94–99].”
Background
Melatonin in Alzheimer's disease and other neurodegenerative disorders
Srinivasan, V. J., Pandi-Perumal, S. R., Cardinali, D. P., Pöeggeler, B., & Hardeland, R. (2006) · Behavioral and Brain Functions · doi:10.1186/1744-9081-2-15 · Cited by 226 · see citing works
Mercury Induces Cell Cytotoxicity and Oxidative Stress and Increases β‐Amyloid Secretion and Tau Phosphorylation in SHSY5Y Neuroblastoma Cells
Olivieri, G., Brack, C., Müller-Spahn, F., Stähelin, H. B., i, M. H., Renard, P., Brockhaus, M., & Hock, C. (2000) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2000.0740231.x · Cited by 210 · see citing works
Attenuation of cold‐induced apoptosis by exogenous melatonin in carrot suspension cells: the possible involvement of polyamines
Lei, X., Zhu, R., Zhang, G., & Dai, Y. (2004) · Journal of Pineal Research · doi:10.1046/j.1600-079x.2003.00106.x · Cited by 200 · see citing works
Antioxidant strategies for Alzheimer's disease
Grundman, M., & Delaney, P. (2002) · Proceedings of The Nutrition Society · doi:10.1079/pns2002146 · Cited by 193 · see citing works
Mechanisms of Melatonin in Alleviating Alzheimer’s Disease
Shukla, M., Govitrapong, P., Boontem, P., Reiter, R., & Satayavivad, J. (2017) · Current Neuropharmacology · doi:10.2174/1570159x15666170313123454 · Cited by 173 · see citing works
“Melatonin significantly reduces cholesterol absorption [171], and the most widely known effect of melatonin on lipids is to prevent their peroxidation [143, 172, 173].”
Background
Anti-amyloidogenic effects of antioxidants: Implications for the prevention and therapeutics of Alzheimer's disease
Ono, K., Hamaguchi, T., Naiki, H., & Yamada, M. (2006) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2006.03.002 · Cited by 183 · see citing works
“Melatonin has demonstrated neuroprotective and antioxidant properties against Aβ mediated oxidative injury in vitro [136, 137].”
Background
Ischemia/reperfusion‐induced arrhythmias in the isolated rat heart: Prevention by melatonin
Tan, D. X., Manchester, L. C., Reiter, R. J., Qi, W., Kim, S. J., & El‐Sokkary, G. H. (1998) · Journal of Pineal Research · doi:10.1111/j.1600-079x.1998.tb00558.x · Cited by 183 · see citing works
The Neuroprotective Effects of Phytoestrogens on Amyloid β Protein-induced Toxicity Are Mediated by Abrogating the Activation of Caspase Cascade in Rat Cortical Neurons
Wang, C., Chi, C., Lin, Y., Chen, C., & Shiao, Y. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m006406200 · Cited by 181 · see citing works
Alzheimer Amyloid β-Peptide Inhibits the Late Phase of Long-Term Potentiation through Calcineurin-Dependent Mechanisms in the Hippocampal Dentate Gyrus
Chen, Q.-S., Wei, W., Shimahara, T., & Xie, C.-W. (2002) · Neurobiology of Learning and Memory · doi:10.1006/nlme.2001.4034 · Cited by 176 · see citing works
Monozygotic twins with Alzheimer's disease treated with melatonin: Case report
Brusco, L. I., Márquez, M., & Cardinali, D. P. (1998) · Journal of Pineal Research · doi:10.1111/j.1600-079x.1998.tb00396.x · Cited by 172 · see citing works
Delivery of pineal melatonin to the brain and SCN: role of canaliculi, cerebrospinal fluid, tanycytes and Virchow–Robin perivascular spaces
Reiter, R. J., Tan, D. X., Kim, S. J., & Cruz, M. H. C. (2014) · Brain Structure and Function · doi:10.1007/s00429-014-0719-7 · Cited by 163 · see citing works
Protective effect of melatonin in a chronic experimental model of Parkinson’s disease
Antolı́n, I., Mayo, J. C., Sainz, R. M., del Brı́o, M. D. L. A., Herrera, F., Martı́n, V., & Rodrı́guez, C. (2002) · Brain Research · doi:10.1016/s0006-8993(02)02551-9 · Cited by 164 · see citing works
Melatonin and Parkinson's Disease
Mayo, J. C., Sainz, R. M., Tan, D., Antolı́n, I., Rodrı́guez, C., & Reiter, R. J. (2005) · Endocrine · doi:10.1385/endo:27:2:169 · Cited by 162 · see citing works
Benzofuran and Indole: Promising Scaffolds for Drug Development in Alzheimer's Disease
Goyal, D., Kaur, A., & Goyal, B. (2018) · ChemMedChem · doi:10.1002/cmdc.201800156 · Cited by 157 · see citing works
Involvement of Oxidative Stress on the Impairment of Energy Metabolism Induced by Aβ Peptides on PC12 Cells: Protection by Antioxidants
Pereira, C., Santos, M. S., & Oliveira, C. (1999) · Neurobiology of Disease · doi:10.1006/nbdi.1999.0241 · Cited by 156 · see citing works
Melatonin prevents apoptosis induced by 6‐hydroxydopamine in neuronal cells: Implications for Parkinson's disease
Mayo, J. C., Sainz, R. M., Urı́a, H., Antolı́n, I., Esteban, M., & Rodrı́guez, C. (1998) · Journal of Pineal Research · doi:10.1111/j.1600-079x.1998.tb00531.x · Cited by 154 · see citing works
Increased melatonin 1a‐receptor immunoreactivity in the hippocampus of Alzheimer's disease patients
Savaskan, E., Olivieri, G., Meier, F., Brydon, L., Jockers, R., Ravid, R., Wirz‐Justice, A., & Müller-Spahn, F. (2002) · Journal of Pineal Research · doi:10.1034/j.1600-079x.2002.00841.x · Cited by 149 · see citing works
“Cell culture experiments have shown that melatonin also prevents Ab-induced neurotoxicity (Pappolla et al., 1997, 2000).”
Background
Induction of NF-κB Activity during Haloperidol-Induced Oxidative Toxicity in Clonal Hippocampal Cells: Suppression of NF-κB and Neuroprotection by Antioxidants
Post, A., Holsboer, F., & Behl, C. (1998) · Journal of Neuroscience · doi:10.1523/jneurosci.18-20-08236.1998 · Cited by 146 · see citing works
Glial cell survival is enhanced during melatonin-induced neuroprotection against cerebral ischemia
Borlongan, C. V. (2000) · The FASEB Journal · doi:10.1096/fj.14.10.1307 · Cited by 144 · see citing works
Melatonin and aging: prospects for human treatment.
Bubenik, G. A., & Konturek, S. J. (2011) · PubMed · Cited by 143 · see citing works
Orally administered melatonin reduces oxidative stress and proinflammatory cytokines induced by amyloid‐β peptide in rat brain: a comparative, in vivo study versus vitamin C and E
Rosales‐Corral, S., Tan, D. X., Reiter, R. J., Valdivia‐Velázquez, M., Martínez‐Barboza, G., Acosta‐Martínez, J. P., & Ortíz, G. G. (2003) · Journal of Pineal Research · doi:10.1034/j.1600-079x.2003.00057.x · Cited by 143 · see citing works
“Melatonin has been tested against Ab in vitro [19, 20, 21], and the current findings also show it to be neuroprotective against Ab-induced oxidative stress including lipid peroxidation in vivo.”
Background
Melatonin in Alzheimer’s Disease: A Latent Endogenous Regulator of Neurogenesis to Mitigate Alzheimer’s Neuropathology
Hossain, M. F., Uddin, M. S., Uddin, G. M. S., Sumsuzzman, D. M., Islam, M. S., Barreto, G. E., Mathew, B., & Ashraf, G. M. (2019) · Molecular Neurobiology · doi:10.1007/s12035-019-01660-3 · Cited by 135 · see citing works
Prospects of the Clinical Utilization of Melatonin
Bubenik, G. A., Blask, D. E., Brown, G. M., Maestroni, G. J. M., Pang, S. F., Reiter, R. J., Viswanathan, M., & Zisapel, N. (1998) · Neurosignals · doi:10.1159/000014545 · Cited by 136 · see citing works
Antioxidant properties of melatonin—an emerging mystery
Beyer, C. E., Steketee, J. D., & Saphier, D. (1998) · Biochemical Pharmacology · doi:10.1016/s0006-2952(98)00180-4 · Cited by 135 · see citing works
Excitotoxicity, Oxidative Stress, and the Neuroprotective Potential of Melatonin
Skaper, S. D., Floreani, M., Ceccon, M., Facci, L., & Giusti, P. (1999) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1999.tb07985.x · Cited by 135 · see citing works
Glutathione elevation by γ‐glutamyl cysteine ethyl ester as a potential therapeutic strategy for preventing oxidative stress in brain mediated by in vivo administration of adriamycin: Implication for chemobrain
Gururaj Joshi, A., Hardas, S. S., Rukhsana Sultana, A., Clair, D. K. S., Vore, M. E., & Butterfield, D. A. (2006) · Journal of Neuroscience Research · doi:10.1002/jnr.21158 · Cited by 134 · see citing works
“, 1992), vitamin C, melatonin (Pappolla et al., 1997), ginko biloba (Smith and Luo, 2003), steroid hormones (Goodman et al.”
Background
Oxidative Stress, Antioxidants and Neurodegenerative Diseases
Casetta, I., Govoni, V., & Granieri, E. (2005) · Current Pharmaceutical Design · doi:10.2174/1381612054065729 · Cited by 134 · see citing works
Possible antioxidant mechanism in melatonin reversal of aging and chronic ethanol-induced amnesia in plus-maze and passive avoidance memory tasks
Vasudeva, R., & Kulkarni, S. K. (2001) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(00)00447-0 · Cited by 130 · see citing works
Olanzapine protects PC12 cells from oxidative stress induced by hydrogen peroxide
Wei, Z., Bai, O., Richardson, J. S., Mousseau, D. D., & Li, X. (2003) · Journal of Neuroscience Research · doi:10.1002/jnr.10668 · Cited by 129 · see citing works
“Reducing SOD-1 activity, either by downregulating SOD-1 with antisense oligonucleotides or by inhibiting SOD-1 with diethyldithiocarbamic acid, induces apoptotic degeneration in neuronal cultures (Rothstein et al., 1994; Pappolla et al., 1997).”
Background
Melatonin reduces memory changes and neural oxidative damage in mice treated with D ‐galactose
Shen, Y., Xu, S., Wei, W., Sun, X., Yang, J., Liu, L., & Chen, D. (2002) · Journal of Pineal Research · doi:10.1034/j.1600-079x.2002.1o850.x · Cited by 127 · see citing works
“Also melatonin is effective in reducing amyloid b-induced lipid peroxidation in vitro [30, 31] as well as in vivo (unpublished data).”
Background
Protective effect of melatonin on β-amyloid-induced apoptosis in rat astroglioma c6 cells and its mechanism
Zheng, F., & Zhang, J. (2004) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2004.08.023 · Cited by 126 · see citing works
Impaired hippocampal long-term potentiation in melatonin MT2 receptor-deficient mice
Larson, J., Jessen, R. E., Uz, T., Arslan, A. D., Kürtüncü, M., Imbesi, M., & Manev, H. (2005) · Neuroscience Letters · doi:10.1016/j.neulet.2005.09.040 · Cited by 123 · see citing works
Indoles as essential mediators in the gut-brain axis. Their role in Alzheimer's disease
Pappolla, M. A., Perry, G. L., Fang, X., Zagorski, M. G., Sambamurti, K., & Pöeggeler, B. (2021) · Neurobiology of Disease · doi:10.1016/j.nbd.2021.105403 · Cited by 122 · see citing works
Extension of life span and stress resistance of Drosophila melanogaster by long-term supplementation with melatonin
Bonilla, E., Medina-Leendertz, S., & Díaz, S. V. (2002) · Experimental Gerontology · doi:10.1016/s0531-5565(01)00229-7 · Cited by 120 · see citing works
A Systematic, Updated Review on the Antidepressant Agomelatine Focusing on its Melatonergic Modulation
Fornaro, M., Prestía, D., Colicchio, S., & Perugi, G. (2010) · Current Neuropharmacology · doi:10.2174/157015910792246227 · Cited by 119 · see citing works
“Melatonin also inhibits the aggregation of the amyloid beta protein into neurotoxic micro-aggregates which seem to underlie the neurotoxicity of this protein, causing neuronal death and formation of neurofibrillary tangles, which are the other neuropathological landmark of Alzheimer's disease [90].”
Background
Two neuronal cell lines expressing the myelin basic protein gene display differences in their in vitro survival and in their response to glia
Bongarzone, E. R., Foster, L. M., Byravan, S., Casaccia‐Bonnefil, P., Schonmann, V., & Campagnoni, A. T. (1998) · Journal of Neuroscience Research · doi:10.1002/(sici)1097-4547(19981101)54:3 · Cited by 21 · see citing works
Alterations in the circadian rhythm of salivary melatonin begin during middle‐age
Zhou, J., Liu, R., van Heerikhuize, J. J., Hofman, M. A., & Swaab, D. F. (2002) · Journal of Pineal Research · doi:10.1034/j.1600-079x.2003.01897.x · Cited by 112 · see citing works
The Melatonin Conformer Space: Benchmark and Assessment of Wave Function and DFT Methods for a Paradigmatic Biological and Pharmacological Molecule
Fogueri, U. R., Kozuch, S., Karton, A., & Martin, J. M. L. (2013) · The Journal of Physical Chemistry A · doi:10.1021/jp312644t · Cited by 113 · see citing works
Inhibition of Alzheimer's disease β‐amyloid aggregation, neurotoxicity, and in vivo deposition by nitrophenols: implications for Alzheimer's therapy
Felice, F. G. D., Houzel, J., Garcia-Abreu, J., Louzada, P. R., Afonso, R. C. D. H., Meirelles, M. N. L., Lent, R., Neto, V. M., & Ferreira, S. T. (2001) · The FASEB Journal · doi:10.1096/fj.00-0676fje · Cited by 113 · see citing works
“For example, the pineal hormone, melatonin, has been reported to interact with Aβ, inhibiting fibrillogenesis and neurotoxicity (19, 20).”
Background
Melatonin as a Pharmacological Agent against Neuronal Loss in Experimental Models of Huntington's Disease, Alzheimer's Disease and Parkinsonism
Reiter, R. J., Cabrera, J., Sainz, R. M., Mayo, J. C., Manchester, L. C., & Tan, D. X. (1999) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1999.tb08028.x · Cited by 112 · see citing works
Dietary supplementation with melatonin reduces levels of amyloid beta‐peptides in the murine cerebral cortex
Lahiri, D. K., Chen, D., Ge, Y., Bondy, S. C., & Sharman, E. H. (2004) · Journal of Pineal Research · doi:10.1111/j.1600-079x.2004.00121.x · Cited by 111 · see citing works
“Thirdly, melatonin prevents death of neuroblastoma cells exposed to the peptide [35], and melatonin promotes nerve growth factor (NGF)-mediated neuronal differentiation in cell cultures [36].”
Background
Alpha-Secretase ADAM10 Regulation: Insights into Alzheimer’s Disease Treatment
Peron, R., Vatanabe, I. P., Manzine, P. R., Camins, A., & Cominetti, M. R. (2018) · Pharmaceuticals · doi:10.3390/ph11010012 · Cited by 111 · see citing works
On the central role of mitochondria dysfunction and oxidative stress in Alzheimer’s disease
Tobore, T. O. (2019) · Neurological Sciences · doi:10.1007/s10072-019-03863-x · Cited by 110 · see citing works
Indian Medicinal Herbs and Formulations for Alzheimer’s Disease, from Traditional Knowledge to Scientific Assessment
Mehla, J., Gupta, P., Pahuja, M., Diwan, D., & Diksha, D. (2020) · Brain Sciences · doi:10.3390/brainsci10120964 · Cited by 108 · see citing works
“Studies have also rep rted that antioxidants protect against Aβ induced neuronal toxicity [16,17].”
Background
Efficient Host–Guest Energy Transfer in Polycationic Cyclophane–Perylene Diimide Complexes in Water
Ryan, S. T. J., del Barrio, J., Ghosh, I., Biedermann, F., Lazar, A. I., Lan, Y., Coulston, R. J., Nau, W. M., & Scherman, O. A. (2014) · Journal of the American Chemical Society · doi:10.1021/ja5032437 · Cited by 109 · see citing works
Protective effect of melatonin in a model of traumatic brain injury in mice
Mésenge, C., Margaill, I., VERRECCHIA, C., Allix, M., Boulu, R. G., & Plotkine, M. (1998) · Journal of Pineal Research · doi:10.1111/j.1600-079x.1998.tb00384.x · Cited by 109 · see citing works
Reciprocal interactions between sleep, circadian rhythms and Alzheimer's disease: Focus on the role of hypocretin and melatonin
Slats, D., Claassen, J. A. H. R., Verbeek, M. M., & Overeem, S. (2012) · Ageing Research Reviews · doi:10.1016/j.arr.2012.04.003 · Cited by 109 · see citing works
Effect of chronic treatment of melatonin on learning, memory and oxidative deficiencies induced by intracerebroventricular streptozotocin in rats
Sharma, M., & Gupta, Y. K. (2001) · Pharmacology Biochemistry and Behavior · doi:10.1016/s0091-3057(01)00611-6 · Cited by 107 · see citing works
Ergothioneine rescues PC12 cells from β-amyloid-induced apoptotic death
Jang, J.-H., Aruoma, O. I., Jen, L.-S., Chung, H. Y., & Surh, Y.-J. (2004) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2003.11.005 · Cited by 112 · see citing works
Melatonin protects human retinal pigment epithelial (RPE) cells against oxidative stress
Liang, F.-Q., Green, L., Wang, C., Alssadi, R., & Godley, B. F. (2004) · Experimental Eye Research · doi:10.1016/j.exer.2004.02.003 · Cited by 106 · see citing works
N‐acetyl‐serotonin (normelatonin) and melatonin protect neurons against oxidative challenges and suppress the activity of the transcription factor NF‐κB
Lezoualc’h, F., Sparapani, M., & Behl, C. (1998) · Journal of Pineal Research · doi:10.1111/j.1600-079x.1998.tb00530.x · Cited by 105 · see citing works
Acteoside inhibits apoptosis in D-Galactosamine and lipopolysaccharide-induced liver injury
Xiong, Q., Hase, K., Tezuka, Y., Namba, T., & Kadota, S. (1999) · Life Sciences · doi:10.1016/s0024-3205(99)00263-5 · Cited by 104 · see citing works
Strategy to reduce free radical species in Alzheimer’s disease: an update of selected antioxidants
Domenico, F. D., Barone, E., Marzia Perluigi, A., & Butterfield, D. A. (2014) · Expert Review of Neurotherapeutics · doi:10.1586/14737175.2015.955853 · Cited by 102 · see citing works
“Melatonin also averted Ab-induced increased intracellular Ca and lipid peroxidation [207], thus suggesting melatonin as a potential therapeutic approach in AD.”
Background
Current advances in the treatment of Alzheimer's disease: focused on considerations targeting Aβ and tau
Yang, H., Sun, Z., & Chen, S. (2012) · Translational Neurodegeneration · doi:10.1186/2047-9158-1-21 · Cited by 102 · see citing works
“was the demonstration that this neurohormone prevents neuronal death caused by exposure to the amyloid beta protein [54].”
Background
Melatonin regulates glucocorticoid receptor: an answer to its antiapoptotic action in thymus
Sainz, R. M., Mayo, J. C., Reiter, R. J., Antolı́n, I., Esteban, M. M., & Rodrı́guez, C. (1999) · The FASEB Journal · doi:10.1096/fasebj.13.12.1547 · Cited by 101 · see citing works
“The most recently described properties of melatonin are 1) its antioxidant capability, acting both as a free radical scavenger (11, 12) and a stimulator of activity (13, 14) and mRNA levels for several antioxidant enzymes (8, 15, 16) and 2) its antiapoptotic effects in thymocytes (17, 18) and neuronal cells (16, 19, 2…”
Background
Melatonin reduces oxidative stress and increases gene expression in the cerebral cortex and cerebellum of aluminum‐exposed rats
Esparza, J. L., Gómez, M., Nogués, M. R., Paternain, J. L., Mallol, J., & Domingo, J. L. (2005) · Journal of Pineal Research · doi:10.1111/j.1600-079x.2005.00225.x · Cited by 100 · see citing works
“Melatonin protects neurons against oxidative stress induced by H2O2 and glutamate [15, 17, 42, 43].”
Background
A novel melatonin agonist Neu-P11 facilitates memory performance and improves cognitive impairment in a rat model of Alzheimer' disease
He, P., Ouyang, X.-P., Zhou, S., Yin, W., Tang, C., Laudon, M., & Tian, S. (2013) · Hormones and Behavior · doi:10.1016/j.yhbeh.2013.04.009 · Cited by 98 · see citing works
“, 2001) and exerts neuroprotective and antioxidant properties against Aβ-induced oxidative injury in vitro and in vivo (Matsubara et al., 2003; Pappolla et al., 1997).”
Melatonin prevents increases in neural nitric oxide and cyclic GMP production after transient brain ischemia and reperfusion in the Mongolian gerbil ( Meriones Unguiculatus )
Guerrero, J. M., Reiter, R. J., Ortíz, G. G., Pablos, M. I., Sewerynek, E., & Chuang, J. (1997) · Journal of Pineal Research · doi:10.1111/j.1600-079x.1997.tb00331.x · Cited by 98 · see citing works
Intranasal therapeutic strategies for management of Alzheimer’s disease
Sood, S., Jain, K., & Gowthamarajan, K. (2014) · Journal of drug targeting · doi:10.3109/1061186x.2013.876644 · Cited by 95 · see citing works
“Melatonin, an indole amide neurohormone, secreted by pineal gland has been found to protect neurons against Ab toxicity and inhibit the progressive formation of b-sheets and amyloid fibrils [184,185].”
Background
Oxidative Stress and Aging as Risk Factors for Alzheimer’s Disease and Parkinson’s Disease: The Role of the Antioxidant Melatonin
Tchekalarova, J. D., & Tzoneva, R. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24033022 · Cited by 100 · see citing works
Melatonin maintains adult hippocampal neurogenesis and cognitive functions after irradiation
Manda, K., & Reiter, R. J. (2009) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2009.10.019 · Cited by 95 · see citing works
Apoptosis modulators in the therapy of neurodegenerative diseases
Deigner, H., Haberkorn, U., & Kinscherf, R. (2000) · Expert Opinion on Investigational Drugs · doi:10.1517/13543784.9.4.747 · Cited by 93 · see citing works
“Melatonin, a pineal hormone with established anti-amyloidogenic and anti-oxidant properties, prevents death and oxidative damage of neuroblastoma cells exposed to Alzheimer Aβ peptide [60,61].”
Background
Melatonin reduces oxidative neurotoxicity due to quinolinic acid:
Cabrera, J., Reiter, R. J., Tan, D. X., Qi, W., Sainz, R. M., Mayo, J. C., García, J. J., Kim, S. J., & El‐Sokkary, G. H. (2000) · Neuropharmacology · doi:10.1016/s0028-3908(99)00128-8 · Cited by 94 · see citing works
Melatonin attenuates amyloid beta25–35-induced apoptosis in mouse microglial BV2 cells
Jang, M.-H., Jung, S.-B., Lee, M., Kim, C., Oh, Y.-T., Kang, I., Kim, J., & Kim, E. (2005) · Neuroscience Letters · doi:10.1016/j.neulet.2005.01.003 · Cited by 93 · see citing works
Products of Cu(II)-catalyzed oxidation in the presence of hydrogen peroxide of the 1–10, 1–16 fragments of human and mouse β-amyloid peptide
Kowalik-Jankowska, T., Ruta, M., Wiśniewska, K., Łankiewicz, L., & Dyba, M. (2004) · Journal of Inorganic Biochemistry · doi:10.1016/j.jinorgbio.2004.03.001 · Cited by 92 · see citing works
Treatment of Alzheimer’s Disease: Beyond Symptomatic Therapies
Buccellato, F. R., D’Anca, M., Tartaglia, G. M., Del Fabbro, M., Scarpini, E., & Galimberti, D. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241813900 · Cited by 94 · see citing works
“In addition, melatonin inhibits the β -ﬁbrillogenesis with neuroprotective and antioxidant activities in vitro and in vivo AD models [153,154].”
Background
The neuroprotective activities of melatonin against the Alzheimer β‐protein are not mediated by melatonin membrane receptors
Pappolla, M. A., Simovich, M. J., Bryant‐Thomas, T., Chyan, Y., Pöeggeler, B., Dubocovich, M. L., Bick, R. J., Perry, G. L., Cruz-Sánchez, F., & Smith, M. A. (2002) · Journal of Pineal Research · doi:10.1034/j.1600-079x.2002.1o838.x · Cited by 91 · see citing works
“A large body of data suggests that Ab has neurotoxic properties and that such effects are mediated by oxygen free radicals (Bozner et al., 1997; Pappolla et al., 1997, 1999; Chyan et al., 1999).”
BackgroundMethodInfluential

Melatonin reduces amyloid β‐induced apoptosis in pheochromocytoma (PC12) cells
Feng, Z., & Zhang, J. (2004) · Journal of Pineal Research · doi:10.1111/j.1600-079x.2004.00164.x · Cited by 68 · see citing works
Alzheimer β protein mediated oxidative damage of mitochondrial DNA: Prevention by melatonin
Pappolla, M. A., Chyan, Y., Pöeggeler, B., Bozner, P., Ghiso, J. A., LeDoux, S. P., & Wilson, G. L. (1999) · Journal of Pineal Research · doi:10.1111/j.1600-079x.1999.tb00619.x · Cited by 89 · see citing works
Anti-Amyloidogenic and Anti-Apoptotic Role of Melatonin in Alzheimer Disease
He, H., Dong, W., & Huang, F. P. (2010) · Current Neuropharmacology · doi:10.2174/157015910792246137 · Cited by 83 · see citing works
The neuroprotective activities of melatonin against the Alzheimer β‐protein are not mediated by melatonin membrane receptors
Pappolla, M. A., Simovich, M. J., Bryant‐Thomas, T., Chyan, Y., Pöeggeler, B., Dubocovich, M. L., Bick, R. J., Perry, G. L., Cruz-Sánchez, F., & Smith, M. A. (2002) · Journal of Pineal Research · doi:10.1034/j.1600-079x.2002.1o838.x · Cited by 91 · see citing works
Protective effect of melatonin on β-amyloid-induced apoptosis in rat astroglioma c6 cells and its mechanism
Zheng, F., & Zhang, J. (2004) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2004.08.023 · Cited by 126 · see citing works

Authors: Pappolla, M. A., Sos, M., Omar, R. A., Bick, R. J., Hickson-Bick, D. L. M., Reiter, R. J., Efthimiopoulos, S., & Robakis, N. K.
Affiliations: University of South Alabama (US)
The University of Texas Health Science Center at Houston (US)
University of Louisville (US)
The University of Texas at San Antonio Health Science Center (US)
Icahn School of Medicine at Mount Sinai (US)
ORCID: Pappolla, Miguel A.
Reiter, Russel J.
Efthimiopoulos, Spiros
Venue: The Journal of Neuroscience
Publisher: Society for Neuroscience
Published: 1997-03-01
Volume: 17
Issue: 5
Pages: 1683-1690
ISSN: 0270-6474 (ISSN-L)
1529-2401
DOI: 10.1523/jneurosci.17-05-01683.1997
PMC: PMC6573387
OpenAlex: W2137034584
Cited by: 359
References: 63
Citations by year: 2026: 2 · 2025: 2 · 2024: 4 · 2023: 4 · 2022: 3 · 2021: 4 · 2020: 9 · 2019: 6 · 2018: 12 · 2017: 5 · 2016: 9 · 2015: 7 · 2014: 16 · 2013: 15 · 2012: 14
FWCI: 8.23
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by-nc-sa
creativecommons.org/licenses/by-nc-sa/4.0/ (vor, 184 d)
Locations: Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (5r01ag011130-03)
National Institute on Aging (RF1AG008200, R56AG008200, AG-08200, AG-11130, R01AG008200)
Topics: Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
Keywords: melatonin, Alzheimer's disease, amyloid-beta, neuroblastoma cells, oxidative stress, neurotoxicity, cell death, intracellular calcium, aging, pineal hormone
MeSH terms: Alzheimer Disease, Animals, Antioxidants, Calcium, Ditiocarb, Doxorubicin, Melatonin, Neuroblastoma, Neurons, Peptide Fragments, Peptides, Superoxide Dismutase, Reproducibility of Results, Lipid Peroxidation, Amyloid beta-Peptides, PC12 Cells, Apoptosis, Oxidative Stress, Mice, Rats

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Melatonin Prevents Death of Neuroblastoma Cells Exposed to the Alzheimer Amyloid Peptide

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